tbuckley/cabot-search huggingface dataset:
Neoadjuvant BRAF-targeted therapy for ameloblastoma of the mandible: an organ preservation approach
Authors: Shirly Grynberg, Marilena Vered, Ronnie Shapira-Frommer, Nethanel Asher, Guy Ben-Betzalel, Ronen Stoff, Yael Steinberg, Ninette Amariglio, Gahl Greenberg, Iris Barshack, Amos Toren, Ran Yahalom, Jacob Schachter, Gideon Rechavi, Ariel Hirschhorn, Gadi Abebe Campino
Journal: JNCI Journal of the National Cancer Institute (2023)

Abstract Background Ameloblastoma is a rare odontogenic neoplasm frequently located in the mandible. Standard treatment involves radical bone resection and immediate reconstruction, causing functional, aesthetic, and psychological impairments. The BRAF V600E mutation is present in approximately 80% of mandible ameloblastomas, and BRAF inhibitors have demonstrated sustained responses in unresectable cases. Methods We identified ameloblastoma patients planned for ablative surgery and screened them for BRAF V600E mutation. Neoadjuvant BRAF inhibitors were offered to facilitate jaw preservation surgery. Retrospective data collection encompassed treatment regimens, tolerability, tumor response, and conversion to mandible preservation surgery. Results Between 2017 and 2022, a total of 11 patients received dabrafenib (n = 6) or dabrafenib with trametinib (n = 5). The median age was 19 (range = 10-83) years. Median treatment duration was 10 (range = 3-20) months. All (100%) patients achieved a radiological response. Ten (91%) patients successfully converted to mandible preservation surgery with residual tumor enucleation. One patient attained complete radiological response, and surgery was not performed. Among the 10 surgically treated patients, all exhibited a pathological response, with 4 achieving near complete response and 6 partial response. At a median follow-up of 14 (range = 7-37) months after surgery, 1 case of recurrence was observed. Grade 1-2 adverse effects were reported in 8 (73%) patients, with a single case of grade 3 (hepatitis). Dose modification was necessary for 3 patients, and 4 experienced treatment interruptions, while 1 patient permanently discontinued therapy. Conclusions Neoadjuvant BRAF inhibition may offer a safe and effective strategy for organ preservation in mandible ameloblastoma treatment.
Therapeutic potential of PANoptosis: innate sensors, inflammasomes, and RIPKs in PANoptosomes
Authors: Ankit Pandeya, Thirumala-Devi Kanneganti
Journal: Trends in Molecular Medicine (2023)

The innate immune system initiates cell death pathways in response to pathogens and cellular stress. Cell death can be either non-lytic (apoptosis) or lytic (PANoptosis, pyroptosis, and necroptosis). PANoptosis has been identified as an inflammatory, lytic cell death pathway driven by caspases and RIPKs that is regulated by PANoptosome complexes, making it distinct from other cell death pathways. Several PANoptosome complexes (including ZBP1-, AIM2-, RIPK1-, and NLRP12-PANoptosomes) have been characterized to date. Furthermore, PANoptosis is implicated in infectious and inflammatory diseases, cancers, and homeostatic perturbations. Therefore, targeting its molecular components offers significant potential for therapeutic development. This review covers PANoptosomes and their assembly, PANoptosome-mediated cell death mechanisms, and ongoing progress in developing therapeutics that target PANoptosis.
A pH‐Responsive Virus‐Like Particle as a Protein Cage for a Targeted Delivery
Authors: Kwan‐Jip Kim, Gijeong Kim, Jin‐Ho Bae, Ji‐Joon Song, Hak‐Sung Kim
Journal: Advanced Healthcare Materials (2023)

Abstract A stimuli‐responsive protein self‐assembly offers promising utility as a protein nanocage for biotechnological and medical applications. Herein, the development of a virus‐like particle (VLP) that undergoes a transition between assembly and disassembly under a neutral and acidic pH, respectively, for a targeted delivery is reported. The structure of the bacteriophage P22 coat protein is used for the computational design of coat subunits that self‐assemble into a pH‐responsive VLP. Subunit designs are generated through iterative computational cycles of histidine substitutions and evaluation of the interaction energies among the subunits under an acidic and neutral pH. The top subunit designs are tested and one that is assembled into a VLP showing the highest pH‐dependent structural transition is selected. The cryo‐EM structure of the VLP is determined, and the structural basis of a pH‐triggered disassembly is delineated. The utility of the designed VLP is exemplified through the targeted delivery of a cytotoxic protein cargo into tumor cells in a pH‐dependent manner. These results provide strategies for the development of self‐assembling protein architectures with new functionality for diverse applications.
Primaquine radical cure in patients with Plasmodium falciparum malaria in areas co-endemic for P falciparum and Plasmodium vivax (PRIMA): a multicentre, open-label, superiority randomised controlled trial
Authors: Kamala Thriemer, Tamiru Shibiru Degaga, Michael Christian, Mohammad Shafiul Alam, Megha Rajasekhar, Benedikt Ley, Mohammad Sharif Hossain, Mohammad Golam Kibria, Tedla Teferi Tego, Dagamawie Tadesse Abate, Sophie Weston, Hellen Mnjala, Angela Rumaseb, Ari Winasti Satyagraha, Arkasha Sadhewa, Lydia Vista Panggalo, Lenny L Ekawati, Grant Lee, Rodas Temesgen Anose, Fitsum Getahun Kiros, Julie A Simpson, Amalia Karahalios, Adugna Woyessa, J Kevin Baird, Inge Sutanto, Asrat Hailu, Ric N Price
Journal: The Lancet (2023)

In areas co-endemic for Plasmodium vivax and Plasmodium falciparum there is an increased risk of P vivax parasitaemia following P falciparum malaria. Radical cure is currently only recommended for patients presenting with P vivax malaria. Expanding the indication for radical cure to patients presenting with P falciparum malaria could reduce their risk of subsequent P vivax parasitaemia.
Ubrogepant for the treatment of migraine attacks during the prodrome: a phase 3, multicentre, randomised, double-blind, placebo-controlled, crossover trial in the USA
Authors: David W Dodick, Peter J Goadsby, Todd J Schwedt, Richard B Lipton, Chengcheng Liu, Kaifeng Lu, Sung Yun Yu, Lawrence Severt, Michelle Finnegan, Joel M Trugman
Journal: The Lancet (2023)
Emergency Department point-of-care antiviral host response testing is accurate during periods of multiple respiratory virus co-circulation
Authors: Nathan J. Brendish, Cai Davis, Mary E. Chapman, Florina Borca, Daniel Waddington, Christopher Hill, Nicola White, Tristan W. Clark
Journal: Journal of Infection (2023)

FebriDx is a CE-marked, FDA-approved point-of-care test that detects the antiviral host response protein Myxovirus Resistance Protein A (MxA), in addition to C-reactive protein, using finger-prick blood. FebriDx MxA detection had a high negative predictive value for COVID-19 in symptomatic adults presenting to hospital in the first waves of the pandemic and was used subsequently as a 'rule out' triage tool in Emergency departments. The diagnostic accuracy of FebriDx MxA in the current context of co-circulation of influenza, SARS-CoV-2, and Respiratory Syncytial Virus (RSV), and in the era of COVID-19 vaccination, is unknown.
Neurological adverse events related to immune-checkpoint inhibitors in Spain: a retrospective cohort study
Authors: Elianet Fonseca, Jose M Cabrera-Maqueda, Raquel Ruiz-García, Laura Naranjo, Carmen Diaz-Pedroche, Roser Velasco, Adrià Macias-Gómez, Jose C Milisenda, Elena Muñoz-Farjas, Elba Pascual-Goñi, Jaime Gállego Perez-Larraya, Albert Saiz, Josep Dalmau, Yolanda Blanco, Francesc Graus, Eugenia Martinez-Hernandez, Iban Aldecoa, Maria Ines Barcelo, Beatrice Canneti, Susana Cedres, Alba Chavarria, Carles Fabregat-Franco, Maria Ferrer-Civeira, Maria Teresa Frutos-Alegria, Mar Guasp, Lamberto Landete, Sara Llufriu, Maria Teresa Marti, Jose Enrique Martinez-Rodriguez, Ana Matas-Garcia, Silvia Moreno-Pulido, Ana Lara Pelayo-Negro, Maria Reig, Javier Riancho, Cristina Sánchez-Vizcaíno, Marco Sanduzzi-Zamparelli, Maria Sepulveda, Saul Silvarrey-Rodriguez, Paula Tagliani
Journal: The Lancet Neurology (2023)
Engineering large and geometrically controlled vascularized nerve tissue in collagen hydrogels to restore large-sized volumetric muscle loss
Authors: Shih-Yen Wei, Po-Yu Chen, Chia-Chang Hsieh, Yu-Shan Chen, Tzu-Hsuan Chen, Yu-Shan Yu, Min-Chun Tsai, Ren-Hao Xie, Guan-Yu Chen, Gung-Chian Yin, Juan M. Melero-Martin, Ying-Chieh Chen
Journal: Biomaterials (2023)
Classic ketogenic diet versus further antiseizure medicine in infants with drug-resistant epilepsy (KIWE): a UK, multicentre, open-label, randomised clinical trial
Authors: Natasha E Schoeler, Louise Marston, Laura Lyons, Sally Halsall, Ruchika Jain, Siobhan Titre-Johnson, Maryam Balogun, Simon J R Heales, Simon Eaton, Michael Orford, Elizabeth Neal, Colin Reilly, Christin Eltze, Elma Stephen, Andrew A Mallick, Finbar O’Callaghan, Shakti Agrawal, Alasdair Parker, Martin Kirkpatrick, Andreas Brunklaus, Ailsa McLellan, Helen McCullagh, Rajib Samanta, Rachel Kneen, Hui Jeen Tan, Anita Devlin, Manish Prasad, Rohini Rattihalli, Helen Basu, Archana Desurkar, Ruth Williams, Penny Fallon, Irwin Nazareth, Nick Freemantle, J Helen Cross
Journal: The Lancet Neurology (2023)

Many infancy-onset epilepsies have poor prognosis for seizure control and neurodevelopmental outcome. Ketogenic diets can improve seizures in children older than 2 years and adults who are unresponsive to antiseizure medicines. We aimed to establish the efficacy of a classic ketogenic diet at reducing seizure frequency compared with further antiseizure medicine in infants with drug-resistant epilepsy.
Anti-CD19 CAR T cells for refractory myasthenia gravis
Authors: Aiden Haghikia, Tobias Hegelmaier, Denise Wolleschak, Martin Böttcher, Christiane Desel, Dominic Borie, Jeremias Motte, Georg Schett, Roland Schroers, Ralf Gold, Dimitrios Mougiakakos
Journal: The Lancet Neurology (2023)
Improving safeguarding of unaccompanied migrant young people
Authors: Susanna Corona Maioli, Amy Stevens, Alexandra Cardoso Pinto, Leni Linthout, Delan Devakumar
Journal: BMJ (2023)

Multidisciplinary organisations working with unaccompanied asylum seeking young people must improve training, coordination, and support to ensure that none are left behind, write Susanna Corona Maioli and colleagues
Flashback Foreword: Oxaliplatin Plus LV5FU2 in Colorectal Cancer
Authors: Robert J. Mayer
Journal: Journal of Clinical Oncology (2023)

Article Tools FLASHBACK FOREWORD Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES JCO Flashback: Exploring an Effective Drug Combination for Colorectal Cancer (2000). November 15, 2023 Leucovorin and Fluorouracil With or Without Oxaliplatin as First-Line Treatment in Advanced Colorectal Cancer. November 15, 2023 ARTICLE CITATION DOI: 10.1200/JCO.23.01109 Journal of Clinical Oncology - published online before print November 15, 2023 PMID: 37967514 Flashback Foreword: Oxaliplatin Plus LV5FU2 in Colorectal Cancer Robert J. Mayer, MD1,2xRobert J. MayerSearch for articles by this author Show More 1Former Associate Editor, Journal of Clinical Oncology, Alexandria, VA2Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA https://doi.org/10.1200/JCO.23.01109 First Page Full Text PDF Figures and Tables © 2023 by American Society of Clinical OncologyTHE TAKEAWAYIn 2000, de Gramont et al1 published data showing that the addition of oxaliplatin to infusional fluorouracil/leucovorin (FOLFOX) enhanced the likelihood of disease regression and prolonged median progression-free survival when used as the initial treatment for measurable, unresectable/metastatic colorectal cancer. The use of FOLFOX was subsequently extended to the adjuvant treatment of stage III colorectal cancer and several other types of gastrointestinal malignancies, in addition to becoming the backbone for the fluorouracil, leucovorin, irinotecan, and oxaliplatin regimen in the treatment of pancreatic cancer. It remains a widely used standard today, in large part because of this trial.AUTHOR'S DISCLOSURES OF POTENTIAL CONFLICTS OF INTERESTFlashback Foreword: Oxaliplatin Plus LV5FU2 in Colorectal CancerThe following represents disclosure information provided by the author of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).Robert J. MayerConsulting or Advisory Role: EisaiNo other potential conflicts of interest were reported. Companion JCO Flashback: Exploring an Effective Drug Combination for Colorectal Cancer (2000) Leucovorin and Fluorouracil With or Without Oxaliplatin as First-Line Treatment in Advanced Colorectal Cancer
Leucovorin and Fluorouracil With or Without Oxaliplatin as First-Line Treatment in Advanced Colorectal Cancer
Authors: A. de Gramont, A. Figer, M. Seymour, M. Homerin, A. Hmissi, J. Cassidy, C. Boni, H. Cortes-Funes, A. Cervantes, G. Freyer, D. Papamichael, N. Le Bail, C. Louvet, D. Hendler, F. de Braud, C. Wilson, F. Morvan, A. Bonetti
Journal: Journal of Clinical Oncology (2023)

In a previous study of treatment for advanced colorectal cancer, the LV5FU2 regimen, comprising leucovorin (LV) plus bolus and infusional fluorouracil (5FU) every 2 weeks, was superior to the standard North Central Cancer Treatment Group/Mayo Clinic 5-day bolus 5FU/LV regimen. This phase III study investigated the effect of combining oxaliplatin with LV5FU2, with progression-free survival as the primary end point.
Tumor diagnosis using carbon-based quantum dots: Detection based on the hallmarks of cancer
Authors: Hang Wang, Siwei Yang, Liangfeng Chen, Yongqiang Li, Peng He, Gang Wang, Hui Dong, Peixiang Ma, Guqiao Ding
Journal: Bioactive Materials (2023)

Carbon-based quantum dots (CQDs) have been shown to have promising application value in tumor diagnosis. Their use, however, is severely hindered by the complicated nature of the nanostructures in the CQDs. Furthermore, it seems impossible to formulate the mechanisms involved using the inadequate theoretical frameworks that are currently available for CQDs. In this review, we re-consider the structure-property relationships of CQDs and summarize the current state of development of CQDs-based tumor diagnosis based on biological theories that are fully developed. The advantages and deficiencies of recent research on CQDs-based tumor diagnosis are thus explained in terms of the manifestation of nine essential changes in cell physiology. This review makes significant progress in addressing related problems encountered with other nanomaterials.
Improving Trauma-Informed Care in the Face of Firearm Violence
Authors: Lynquell Biggs, Franklin Cosey-Gay, Sonya Mathies Dinizulu, Divontae Harper, Jazmin King, Athena Mitchell, Memory Pines, Selwyn O. Rogers, Bradley Stolbach
Journal: New England Journal of Medicine (2023)

In this Double Take video from the New England Journal of Medicine, Drs. Franklin Cosey-Gay, Sonya Mathies Dinizulu, Selwyn O. Rogers, Jr., and Bradley Stolbach (University of Chicago) meet with members of REACT (Recovery Empowerment after Community Trauma) to discuss continuous traumatic stress from community violence in terms of its effects on health, its root causes, and how medical providers can better support survivors of violence. They also discuss ways in which the medical community can work toward prevention of community violence and strengthen patient advocacy outside the hospital.
Case 35-2023: A 38-Year-Old Woman with Waxing and Waning Pulmonary Nodules
Authors: Jessica B. McCannon, Jo-Anne O. Shepard, Alexandra K. Wong, Molly F. Thomas, T. Leif Helland
Journal: New England Journal of Medicine (2023)

A 38-year-old woman was evaluated because of dyspnea, chest discomfort, and waxing and waning pulmonary nodules. A diagnosis was made.
Two Phase 3 Trials of Gantenerumab in Early Alzheimer’s Disease
Authors: Randall J. Bateman, Janice Smith, Michael C. Donohue, Paul Delmar, Rachid Abbas, Stephen Salloway, Jakub Wojtowicz, Kaj Blennow, Tobias Bittner, Sandra E. Black, Gregory Klein, Mercè Boada, Timo Grimmer, Akira Tamaoka, Richard J. Perry, R. Scott Turner, David Watson, Michael Woodward, Angeliki Thanasopoulou, Christopher Lane, Monika Baudler, Nick C. Fox, Jeffrey L. Cummings, Paulo Fontoura, Rachelle S. Doody
Journal: New England Journal of Medicine (2023)

Monoclonal antibodies that target amyloid-beta (Aβ) have the potential to slow cognitive and functional decline in persons with early Alzheimer's disease. Gantenerumab is a subcutaneously administered, fully human, anti-Aβ IgG1 monoclonal antibody with highest affinity for aggregated Aβ that has been tested for the treatment of Alzheimer's disease. Download a PDF of the Research Summary. We conducted two phase 3 trials (GRADUATE I and II) involving participants 50 to 90 years of age with mild cognitive impairment or mild dementia due to Alzheimer's disease and evidence of amyloid plaques on positron-emission tomography (PET) or cerebrospinal fluid (CSF) testing. Participants were randomly assigned to receive gantenerumab or placebo every 2 weeks. The primary outcome was the change from baseline in the score on the Clinical Dementia Rating scale–Sum of Boxes (CDR-SB; range, 0 to 18, with higher scores indicating greater cognitive impairment) at week 116. A total of 985 and 980 participants were enrolled in the GRADUATE I and II trials, respectively. The baseline CDR-SB score was 3.7 in the GRADUATE I trial and 3.6 in the GRADUATE II trial. The change from baseline in the CDR-SB score at week 116 was 3.35 with gantenerumab and 3.65 with placebo in the GRADUATE I trial (difference, –0.31; 95% confidence interval [CI], –0.66 to 0.05; P=0.10) and was 2.82 with gantenerumab and 3.01 with placebo in the GRADUATE II trial (difference, –0.19; 95% CI, –0.55 to 0.17; P=0.30). At week 116, the difference in the amyloid level on PET between the gantenerumab group and the placebo group was –66.44 and –56.46 centiloids in the GRADUATE I and II trials, respectively, and amyloid-negative status was attained in 28.0% and 26.8% of the participants receiving gantenerumab in the two trials. Across both trials, participants receiving gantenerumab had lower CSF levels of phosphorylated tau 181 and higher levels of Aβ42 than those receiving placebo; the accumulation of aggregated tau on PET was similar in the two groups. Amyloid-related imaging abnormalities with edema (ARIA-E) occurred in 24.9% of the participants receiving gantenerumab, and symptomatic ARIA-E occurred in 5.0%. Among persons with early Alzheimer's disease, the use of gantenerumab led to a lower amyloid plaque burden than placebo at 116 weeks but was not associated with slower clinical decline. (Funded by F. Hoffmann–La Roche; GRADUATE I and II ClinicalTrials.gov numbers, NCT03444870 and NCT03443973, respectively.) QUICK TAKE VIDEO SUMMARYGantenerumab in Early Alzheimer's Disease 02:01
Arginine or Hypertonic Saline–Stimulated Copeptin to Diagnose AVP Deficiency
Authors: Julie Refardt, Cihan Atila, Irina Chifu, Emanuele Ferrante, Zoran Erlic, Juliana B. Drummond, Rita Indirli, Roosmarijn C. Drexhage, Clara O. Sailer, Andrea Widmer, Susan Felder, Andrew S. Powlson, Nina Hutter, Deborah R. Vogt, Mark Gurnell, Beatriz S. Soares, Johannes Hofland, Felix Beuschlein, Martin Fassnacht, Bettina Winzeler, Mirjam Christ-Crain
Journal: New England Journal of Medicine (2023)

Distinguishing between arginine vasopressin (AVP) deficiency and primary polydipsia is challenging. Hypertonic saline–stimulated copeptin has been used to diagnose AVP deficiency with high accuracy but requires close sodium monitoring. Arginine-stimulated copeptin has shown similar diagnostic accuracy but with a simpler test protocol. However, data are lacking from a head-to-head comparison between arginine-stimulated copeptin and hypertonic saline–stimulated copeptin in the diagnosis of AVP deficiency. Download a PDF of the Research Summary. In this international, noninferiority trial, we assigned adult patients with polydipsia and hypotonic polyuria or a known diagnosis of AVP deficiency to undergo diagnostic evaluation with hypertonic-saline stimulation on one day and with arginine stimulation on another day. Two endocrinologists independently made the final diagnosis of AVP deficiency or primary polydipsia with use of clinical information, treatment response, and the hypertonic-saline test results. The primary outcome was the overall diagnostic accuracy according to prespecified copeptin cutoff values of 3.8 pmol per liter after 60 minutes for arginine and 4.9 pmol per liter once the sodium level was more than 149 mmol per liter for hypertonic saline. Of the 158 patients who underwent the two tests, 69 (44%) received the diagnosis of AVP deficiency and 89 (56%) received the diagnosis of primary polydipsia. The diagnostic accuracy was 74.4% (95% confidence interval [CI], 67.0 to 80.6) for arginine-stimulated copeptin and 95.6% (95% CI, 91.1 to 97.8) for hypertonic saline–stimulated copeptin (estimated difference, −21.2 percentage points; 95% CI, −28.7 to −14.3). Adverse events were generally mild with the two tests. A total of 72% of the patients preferred testing with arginine as compared with hypertonic saline. Arginine-stimulated copeptin at a value of 3.0 pmol per liter or less led to a diagnosis of AVP deficiency with a specificity of 90.9% (95% CI, 81.7 to 95.7), whereas levels of more than 5.2 pmol per liter led to a diagnosis of primary polydipsia with a specificity of 91.4% (95% CI, 83.7 to 95.6). Among adult patients with polyuria polydipsia syndrome, AVP deficiency was more accurately diagnosed with hypertonic saline–stimulated copeptin than with arginine-stimulated copeptin. (Funded by the Swiss National Science Foundation; CARGOx ClinicalTrials.gov number, NCT03572166.) QUICK TAKE VIDEO SUMMARYStimulated Copeptin to Diagnose AVP Deficiency 02:22
What the Gantenerumab Trials Teach Us about Alzheimer’s Treatment
Authors: Lon S. Schneider
Journal: New England Journal of Medicine (2023)

An amyloid hypothesis1 for Alzheimer's disease posits that amyloid-beta (Aβ) peptides cleaved from Aβ precursor protein trigger a neurodegenerative cascade, causing cognitive and functional impairment. The peptides have various lengths, ranging from monomers to self-assembled soluble oligomers, insoluble fibrils, and extracellular deposits, or plaques. Any of these species could be toxic. The antiamyloid monoclonal antibodies aducanumab2 and lecanemab3 have been approved by the Food and Drug Administration (FDA) for the treatment of early Alzheimer's disease; donanemab4 seems to be headed for approval. Aducanumab and lecanemab received accelerated approval on the basis of a reduction in amyloid plaques. Lecanemab later received . . .
Testing for Arginine Vasopressin Deficiency
Authors: John Newell-Price
Journal: New England Journal of Medicine (2023)

Accurate classification of patients with hypotonic polyuria is essential because management differs for the three main causes1: arginine vasopressin (AVP) deficiency (formerly called central diabetes insipidus), AVP resistance (also known as nephrogenic diabetes insipidus),2 and primary polydipsia, in which excess fluid intake suppresses AVP secretion. Primary polydipsia is the most common cause of hypotonic polyuria, whereas AVP deficiency is less common. Nerve bodies in the hypothalamus synthesize a prohormone precursor peptide to vasopressin. During axonal transport to termini in the posterior pituitary, this peptide is cleaved to form AVP and a nonactive C-terminal portion, copeptin. AVP and copeptin are then . . .